This research described in this proposal can be segmented into four distinct parts. These include: (a) the development of a synthetic protocol which will permit large scale, enantioselective syntheses of the antiviral agent, 3'-thia-2'-deoxycytidine (BCH-189); (b) the development of a synthetic protocol which will permit large scale, enantioselective syntheses of the anitviral agent, 5-fluoro-3'-thia-2'-deoxycytidine (DLS-022); (c) the preparation and evaluation of a large variety of analogues of 3'-thia-2'deoxycytidine; (d) the preparation and evaluation of other heterocyclic nucleoside analogues, including dioxolanes, dithiolanes, oxathiolanes, imidazolanes, oxazolanes and thiazolanes.